Grey matter correlates of minor physical anomalies in the ÆSOP
                        first-episode psychosis study

BackgroundMinor physical anomalies are more prevalent among people with psychosis. This supports a neurodevelopmental aetiology for psychotic disorders, since these anomalies and the brain are both ectodermally derived. However, little is understood about the brain regions implicated in this association.AimsTo examine the relationship between minor physical anomalies and grey matter structure in a sample of patients with first-episode psychosis.MethodSixty patients underwent assessment of minor physical anomalies with the Lane scale. High-resolution magnetic resonance images and voxel-based methods of image analysis were used to investigate brain structure in these patients.ResultsThe total anomalies score was associated with a grey matter reduction in the prefrontal cortex and precuneus and with a grey matter excess in the basal ganglia, thalamus and lingual gyrus.ConclusionsMinor physical anomalies in a sample of patients with first-episode psychosis are associated with regional grey matter changes. These regional changes may be important in the pathogenesis of psychotic disorder.

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Brain structural abnormalities in first episode psychosis: A multimodal analysis

European Psychiatry ◽

10.1016/s0924-9338(11)72655-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 950-950

Author(s):

S. Rigucci ◽

A. Comparelli ◽

A. De Carolis ◽

M.C. Rossi-Espagnet ◽

E. Ambrosi ◽

...

Keyword(s):

Grey Matter ◽

Diffusion Tensor ◽

First Episode Psychosis ◽

Magnetic Resonance Images ◽

Facial Affect ◽

First Episode ◽

Affect Recognition ◽

Facial Affect Recognition ◽

Data Set ◽

Episode Psychosis

IntroductionWhite matter abnormalities play a prominent role in the pathogenesis of schizophrenia. Diffusion tensor imaging (DTI) studies showed a widespread decrease in fractional anisotropy (FA) in psychotic disorders.AimsTo examine white and grey matter abnormalities in first episode psychosis (FEP).MethodsWe obtained T1-weighted and DTI magnetic resonance images (1.5 T) from 8 right-handed drug-naïve FEP patients and 8 healthy controls. The DTI data set was used to calculate FA maps; we carried-out optimized voxel-based morphometry (VBM) analysis of grey matter (GM) and FA maps using SPM2.Patients were assessed with a neuropsychological battery comprising the Trail Making Test, the Stroop Colour Word Test, the Wisconsin Card Sorting Test and a test of Facial Affect recognition.ResultsThe voxelwise analysis showed decreased FA in the superior longitudinal and inferior fronto-occipital fasciculi, bilaterally, and in the left uncinate fasciculus. We observed reduced GM volume in the left frontal cortex (Brodmann areas [BA] 47, 13, 11, 10, and 9) and in right frontal (BA6), temporal (BA34) and occipital (BA 18, 19, and 30) cortex.Neuropsychological assessment showed impaired executive function and deficit in facial affect recognition.ConclusionOur findings showed fronto-temporal disconnectivity in FEP and structural alterations in both cortical and subcortical regions.Neuroanatomical findings are consistent with patients’ neuropsychological performance.Further studies to establish a relationship between white and grey matter disarray on one hand and neuropsychological testing are needed.

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QUALITY OF INDIVIDUAL AND GROUP LEVEL INTERVENTIONS FOR FIRST EPISODE PSYCHOSIS AT THE TERTIARY PSYCHIATRIC HOSPITAL IN UGANDA.

10.31234/osf.io/hrygs ◽

2020 ◽

Author(s):

Emmanuel Kiiza Mwesiga ◽

Noeline Nakasujja ◽

Lawrence Nankaba ◽

Juliet Nakku ◽

Seggane Musisi

Keyword(s):

Psychiatric Hospital ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Group Level ◽

Group Interventions ◽

Episode Psychosis ◽

Essential Components ◽

The Individual

Introduction: Individual and group level interventions have the largest effect on outcomes in patients with the first episode of psychosis. The quality of these individual and group level interventions provided to first-episode psychosis patients in Uganda is unclear.Methods: The study was performed at Butabika National Psychiatric Teaching and referral hospital in Uganda. A retrospective chart review of recently discharged adult in-patients with the first episode of psychosis was first performed to determine the proportion of participants who received the different essential components for individual and group level interventions. From the different proportions, the quality of the services across the individual and group interventions was determined using the first-Episode Psychosis Services Fidelity Scale (FEPS-FS). The FEPS-FS assigns a grade of 1-5 on a Likert scale depending on the proportion of patients received the different components of the intervention. Results: The final sample included 156 first-episode psychosis patients. The median age was 27 years [IOR (24-36)] with 55% of participants of the female gender. 13 essential components across the individual and group interventions were assessed and their quality quantified. All 13 essential components had poor quality with the range of scores on the FEPS-FS of 1-3. Only one essential component assessed (use of single antipsychotics) had moderate quality.Discussion: Among current services at the National psychiatric hospital of Uganda, the essential for individual and group level interventions for psychotic disorders are of low quality. Further studies are required on how the quality of these interventions can be improved.

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Conceptual disorganization and redistribution of resting state cortical hubs in untreated first episode psychosis: A 7T MRI study

10.31234/osf.io/rzvby ◽

2020 ◽

Author(s):

Avyarthana Dey ◽

Kara Dempster ◽

Michael Mackinley ◽

Peter Jeon ◽

Tushar Das ◽

...

Keyword(s):

Negative Symptoms ◽

Superior Temporal Gyrus ◽

Brain Regions ◽

First Episode Psychosis ◽

Cortical Reorganization ◽

First Episode ◽

Formal Thought Disorder ◽

Whole Brain ◽

Episode Psychosis ◽

Positive And Negative Symptoms

Background:Network level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype which predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs).Methods:We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs and characterized the patterns of network connectivity in the two groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity.Results:Compared to HCs, reduced hubness of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased hubness of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. These two regions were strongly correlated with CD scores but not with other symptom scores.Discussion:Our observations are congruent with previous findings of reduced but not increased hubness. We observed increased hubness of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer.Conclusion:These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. A longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

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Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

Molecular Psychiatry ◽

10.1038/s41380-021-01197-9 ◽

2021 ◽

Author(s):

Meike Heurich ◽

Melanie Föcking ◽

David Mongan ◽

Gerard Cagney ◽

David R. Cotter

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Specific Protein ◽

First Episode ◽

Clinical High Risk ◽

Blood Proteins ◽

Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

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Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition

Psychological Medicine ◽

10.1017/s0033291720004201 ◽

2020 ◽

pp. 1-10

Author(s):

Deepak K. Sarpal ◽

Goda Tarcijonas ◽

Finnegan J. Calabro ◽

William Foran ◽

Gretchen L. Haas ◽

...

Keyword(s):

Cognitive Control ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Cognitive State ◽

Cognitive States ◽

Episode Psychosis ◽

Dorsolateral Prefrontal ◽

Parietal Lobule ◽

Context Specific

Abstract Background Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with ‘background connectivity’ following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders. Thus, here we examine background connectivity during executive processing in a cohort of participants with first-episode psychosis (FEP). Methods The following fMRI study examined background connectivity of the dorsolateral prefrontal cortex (DLPFC), during working memory engagement in a group of 43 patients with FEP, relative to 35 healthy controls (HC). Findings were also examined in relation to measures of executive function. Results The FEP group relative to HC showed significantly lower background DLPFC connectivity with bilateral superior parietal lobule (SPL) and left inferior parietal lobule. Background connectivity between DLPFC and SPL was also positively associated with overall cognition across all subjects and in our FEP group. In comparison, resting-state frontoparietal connectivity did not differ between groups and was not significantly associated with overall cognition, suggesting that psychosis-related alterations in executive networks only emerged during states of goal-oriented behavior. Conclusions These results provide novel evidence indicating while frontoparietal connectivity at rest appears intact in psychosis, when engaged during a cognitive state, it is impaired possibly undermining cognitive control capacities in FEP.

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Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

Psychological Medicine ◽

10.1017/s0033291719002277 ◽

2019 ◽

Vol 50 (13) ◽

pp. 2182-2193 ◽

Cited By ~ 11

Author(s):

Kirsten B. Bojesen ◽

Bjørn H. Ebdrup ◽

Kasper Jessen ◽

Anne Sigvard ◽

Karen Tangmose ◽

...

Keyword(s):

Psychotic Disorders ◽

Poor Response ◽

First Episode Psychosis ◽

Anterior Cingulate ◽

First Episode ◽

Antipsychotic Treatment ◽

Resonance Spectroscopy ◽

Reference Levels ◽

Clinical Prognosis ◽

Episode Psychosis

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

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S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.216 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S93-S93

Author(s):

Irina Falkenberg ◽

Huai-Hsuan Tseng ◽

Gemma Modinos ◽

Barbara Wild ◽

Philip McGuire ◽

...

Keyword(s):

High Risk ◽

Emotion Recognition ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Healthy Controls ◽

Emotional Faces ◽

Facial Movements ◽

Episode Psychosis ◽

Ultra High Risk

Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.

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Longitudinal changes in brain metabolites in healthy subjects and patients with first episode psychosis (FEP): a 7-Tesla MRS study

10.1101/2020.08.25.267419 ◽

2020 ◽

Author(s):

Min Wang ◽

Peter B. Barker ◽

Nicola Cascella ◽

Jennifer M. Coughlin ◽

Gerald Nestadt ◽

...

Keyword(s):

Young Adulthood ◽

Brain Regions ◽

First Episode Psychosis ◽

Anterior Cingulate ◽

7 Tesla ◽

First Episode ◽

Resonance Spectroscopy ◽

Invasive Approach ◽

Longitudinal Changes ◽

Episode Psychosis

AbstractObjective7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differences in the age of study participants and duration of illness. This study is the first to report novel longitudinal patterns in young adulthood from both physiological and pathological viewpoints using 7T MRS.MethodsUtilizing a four-year longitudinal cohort with 38 first episode psychosis (FEP) patients (onset within 2 years) and 48 healthy controls (HC), the authors examined the annual percentage changes of 9 neurometabolites in 5 brain regions.ResultsBoth FEP patients and HC subjects were found to have significant longitudinal reductions in glutamate (Glu) in the anterior cingulate cortex (ACC). Only FEP patients were found to have a significant decrease over time in γ-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mI), and total choline (tCho: phosphocholine plus glycerophosphocholine) in the ACC. Uniquely, glutathione (GSH) was found to have a near zero annual percentage change in both FEP patients and HC subjects in all 5 brain regions over a four-year timespan in young adulthood.ConclusionsGSH could be a trait marker for diagnostic applications at least in young adulthood. Glu, GABA, NAA, mI, and tCho in the ACC are associated with the patient’s status and could be state markers for mechanistic studies of psychotic disorders, including those for progressive pathological changes and medication effects in young adulthood.

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Dissection of neuroinflammation in schizophrenia

BJPsych Open ◽

10.1192/bjo.2021.730 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S274-S275

Author(s):

Fizah Muratib ◽

Yuya Mizuno ◽

Ines Carreira Figueiredo ◽

Oliver Howes ◽

Tiago Reis Marques

Keyword(s):

Risk Factor ◽

Grey Matter ◽

Psychotic Disorders ◽

Positive Association ◽

Brain Regions ◽

Regions Of Interest ◽

Cannabis Use ◽

Similar Response ◽

Frequency Of Use ◽

The Brain

AimsSchizophrenia is notoriously becoming one of the world's most debilitating mental disorders, affecting 1 in 100 people. There is increasing evidence that neuroinflammation plays a part in the pathogenesis of schizophrenia and other psychotic disorders; microglial activity acting as a marker for neuroinflammatory reactions in the brain. Furthermore, cannabis is an illicit substance that also evokes a similar response in the neuroimmune activity. This project explores how cannabis exposure influences an elevation in neuroinflammatory responses through TSPO levels, and whether this information can help us determine if cannabis use and increased TSPO levels can be associated with a risk factor for developing psychosis.Method55 participants (36 males and 19 females) were recruited from the community by the IRIS (Inflammatory Reaction in Schizophrenia) team at the IoPPN, King's College London, from which 34 patients with a diagnosis of schizophrenia and 21 healthy controls took part in the study. The eligible participants underwent clinical assessments and PET scanning, from which cannabis use history and PET data were collected. Participant neuroinflammatory levels are represented by [18F]DPA-714 volume and different regions of grey matter in the brain were analysed through multivariate analyses, the confounding variables being age and TSPO genotype.ResultA statistically significant association is shown between participants who have had exposure to cannabis and participants who have not had any exposure in their lifetime. The differences across the prioritised brain regions of interest were robust, the association appearing more apparent and statistically significant in the total (p = .00) and temporal grey matter (p = .00) regions of the brain. This may suggest that cannabis exposure influences the [18F]DPA-714 VT in the significant regions of interest. However, a negative association is seen with current use, the quantity of use, and the frequency of use.ConclusionThe initial findings for cannabis exposure show us a positive association with increased TSPO levels, however, limitations must be taken into account. Although we cannot readily establish that elevated TSPO levels in cannabis users can presently act as a risk factor marker for developing psychosis from this particular study, we can utilise this data to continue our research in disclosing a new system to predict the occurrence of psychosis.

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Circulating lipids associate with future weight gain in individuals with an at-risk mental state and in first-episode psychosis

10.1101/2020.01.30.20019711 ◽

2020 ◽

Author(s):

Santosh Lamichhane ◽

Alex M. Dickens ◽

Partho Sen ◽

Heikki Laurikainen ◽

Jaana Suvisaari ◽

...

Keyword(s):

At Risk ◽

Weight Gain ◽

High Risk ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

Molecular Signature ◽

First Episode ◽

Baseline Serum ◽

Average Life Span ◽

Episode Psychosis

AbstractPatients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic co-morbidities. Identification of individuals with psychotic disorders with a high risk of rapid weight gain, and the associated development of metabolic complications, is an unmet need as regards public health. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 controls (CTR), 44 first-episode psychosis (FEP) patients and 22 individuals at clinical-high-risk (CHR) for psychosis, from two study centers (Turku/Finland and London/UK). Baseline serum samples were analyzed by lipidomics, while body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols with low double bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of two triacylglycerols (TG(48:0) and TG(45:0)), was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals, and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic co-morbidities.

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